Dosing and uses of Lipiodol (ethiodized oil)
Adult dosage forms and strengths
injectable oiL
- 480mg/mL (iodine)
Hysterosalpingography
Inject into the endometrial cavity with fluoroscopic controL
Inject increments of 2 mL until tubal patency is determined; stop the injection if patient develops excessive discomfort
Reimage after 24 hr to establish whether ethiodized oil has entered the peritoneal cavity
Before use, exclude the presence of these conditions: pregnancy, uterine bleeding and endocervicitis, acute pelvic inflammatory disease, the immediate premenstrual or postmenstrual phase, or within 30 days of curettage or conization
Lymphography
Inject into a lymphatic vessel under radiologic guidance to prevent inadvertent venous administration or intravasation
Unilateral lymphography of the upper extremities: 2-4 mL
Unilateral lymphography of the lower extremities: 6-8 mL
Penile lymphography: 2-3 mL
Cervical lymphography: 1-2 mL
Upper or lower extremities administration
- Start the injection into a lymphatic channel at a rate not to exceed 0.2 mL/min
- Inject the total dose in no less than 1.25 hr
- Use frequent radiologic monitoring to determine the appropriate injection rate and to follow the progress within the lymphatics
- Interrupt the injection if the patient experiences pain
- Terminate the injection if lymphatic blockage is present to minimize introduction of ethiodized oil into the venous circulation via lymphovenous channels
- Terminate the injection as soon as ethiodized oil is radiographically evident in the thoracic duct to minimize entry into the subclavian vein and pulmonary embolization
- Obtain immediate postinjection images
- Reimage at 24 or 48 hr to evaluate nodal architecture
Hepatocellular Carcinoma
Selective hepatic intra-arterial use is indicated for imaging tumors in adults with known hepatocellular carcinoma
Determine the dose depending on the tumor size, local blood flow in the liver, and local blood flow in the tumor
Inject from 1.5-15 mL slowly under continuous radiologic monitoring
Stop the injection when stagnation or reflux is evident
Limit the dose to only the quantity required for adequate visualization
Total dose administered should not exceed 20 mL
Dosing Considerations
Screen all patients for renal dysfunction by obtaining history and/or laboratory tests
Administration
Preparation
- Use the smallest possible amount according to the anatomical area to be visualized
- Inspect visually for particulate matter and discoloration before administration
- Do not use the solution if particulate matter is present or if the container appears damaged
- Normal is clear, pale-yellow to amber-colored oil; do not use if the color has darkened
- Draw into a glass syringe and use promptly
- Discard any unused portion of ampoule
- Observe patient for hypersensitivity during injection and for 30 min following
Storage
- Store at controlled room temperature 15-30°C (59-86°F)
- Protect from light
- Remove from carton only upon use
Pediatric dosage forms and strengths
injectable oiL
- 480mg/mL (iodine)
Lymphography
Use the smallest possible amount according to the anatomical area to be visualized
Inject into a lymphatic vessel under radiologic guidance to prevent inadvertent venous administration or intravasation
Inject a minimum of 1 mL to a maximum of 6 mL according to the anatomical area to be visualized
Do not exceed 0.25 mL/kg
Upper or lower extremities administration
- Start the injection into a lymphatic channel at a rate not to exceed 0.2 mL/min
- Inject the total dose in no less than 1.25 hr
- Use frequent radiologic monitoring to determine the appropriate injection rate and to follow the progress within the lymphatics
- Interrupt the injection if the patient experiences pain
- Terminate the injection if lymphatic blockage is present to minimize introduction of ethiodized oil into the venous circulation via lymphovenous channels
- Terminate the injection as soon as ethiodized oil is radiographically evident in the thoracic duct to minimize entry into the subclavian vein and pulmonary embolization
- Obtain immediate postinjection images
- Reimage at 24 or 48 hr to evaluate nodal architecture
Dosing Considerations
Screen all patients for renal dysfunction by obtaining history and/or laboratory tests
Administration
Preparation
- Inspect visually for particulate matter and discoloration before administration
- Do not use the solution if particulate matter is present or if the container appears damaged
- Normal is clear, pale yellow to amber colored oil; do not use if the color has darkened
- Draw into a glass syringe and use promptly
- Discard any unused portion of ampoule
- Observe patient for hypersensitivity during injection and for 30 min following
Storage
- Store at controlled room temperature 15-30°C (59-86°F)
- Protect from light
- Remove from carton only upon use
Lipiodol (ethiodized oil) adverse (side) effects
Postmarketing Reports
Endocrine disorders: Hypothyroidism, hyperthyroidism, thyroiditis
Eye disorders: Retinal vein thrombosis
Gastrointestinal disorders: Nausea, vomiting, diarrhea
General disorders and administration site: Fever, pain, granuloma
Hepatobiliary disorders: Hepatic vein thrombosis
Immune system disorders: Hypersensitivity, anaphylactic reaction, anaphylactoid reaction
Nervous system disorders: Cerebral embolism
Respiratory, thoracic, and mediastinal disorders: Pulmonary embolism, dyspnea, cough, acute respiratory distress syndrome
Urinary system disorders: Renal insufficiency
Hysterosalpingography
- Abdominal pain
- Foreign body reactions
- Exacerbation of pelvic inflammatory disease
Lymphography
- Cardiovascular collapse
- Lymphangitis
- Thrombophlebitis
- Edema or exacerbation of preexisting lymphedema
- Dyspnea and cough
- Fever
- Iodism (headache, soreness of mouth and pharynx, coryza, and rash)
- Allergic dermatitis Lipogranuloma Delayed healing at the site of incision
Hepatic intra-arterial injection
- Common reactions: Fever, abdominal pain, nausea, and vomiting
- Other reactions: Hepatic ischemia, liver enzymes abnormalities, temporary decrease in liver function, liver decompensation, and renal insufficiency
- Procedural risks: Vascular complications and infections
Warnings
Black box warnings
For intralymphatic, intrauterine, and selective hepatic intra-arterial use only
Pulmonary and cerebral embolism can result from inadvertent intravascular injection or intravasation of ethiodized oiL
Inject slowly with radiologic monitoring; do not exceed recommended dose
Contraindications
NOT for IV, IM, IT, or SC use (see Black box warnings)
Hypersensitivity
Hyperthyroidism
Traumatic injuries
Recent hemorrhage or bleeding
Hysterosalpingography
- Pregnancy
- Acute pelvic inflammatory disease
- Marked cervical erosion
- Endocervicitis and intrauterine bleeding In the immediate premenstrual or postmenstrual phase
- Within 30 days of curettage or conization
Lymphography
- Right to left cardiac shunt
- Advanced pulmonary disease
- Tissue trauma or hemorrhage
- Advanced neoplastic disease with expected lymphatic obstruction
- Previous surgery interrupting the lymphatic system
- Radiation therapy to the examined area
Hepatic intra-arterial use
- Areas of the liver where the bile ducts are dilated (unless external biliary drainage was performed before injection)
Cautions
Embolism
- Embolization to lungs, brain, and other major organs may occur
- Pulmonary embolization (PE) may occur immediately or after a few hours to days from inadvertent systemic vascular injection or intravasation; this may cause decreased pulmonary diffusing capacity and pulmonary blood flow, pulmonary infarction, acute respiratory distress syndrome, and fatalities
- Avoid use in patients with severely impaired lung function, cardiorespiratory failure, or right–sided cardiac overload
- Perform radiological monitoring during the injection
- Do not exceed the recommended maximum dose and rate of injection
- During lymphography, minimize the risk of PE by obtaining radiographic confirmation of intralymphatic (rather than venous) injection, and terminate the procedure when ethiodized oil becomes visible in the thoracic duct or lymphatic obstruction is observed
Hypersensitivity reactions
- Anaphylactoid and anaphylactic reactions with cardiovascular, respiratory, or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred
- Avoid use with a history of sensitivity to other iodinated contrast agents, bronchial asthma, or allergic disorders
- Observe patients for signs and symptoms of hypersensitivity reactions during and for at least 30 minutes following administration
Exacerbation of chronic liver disease
- Hepatic intra-arterial injection may exacerbate chronic liver disease conditions including:
- Portal hypertension and cause variceal bleeds due to obstruction of the intrahepatic portal channels by opening a presinusoidal anastomosis
- Hepatic ischemia and cause liver enzyme elevations, fever, and abdominal pain
- Hepatic failure and cause ascites and encephalopathy
- Hepatic vein thrombosis, irreversible liver insufficiency, and fatalities reported
- Procedural risks include vascular complications and infections
Thyroid dysfunction
- Iodinated contrast media can affect thyroid function because of the free iodine content and can cause hyperthyroidism or hypothyroidism in predisposed patients
- Patients at risk are those with latent hyperthyroidism and those with Hashimoto thyroiditis or history of thyroid irradiation
- Ethiodized oil may remain in the body for several months; therefore, thyroid diagnostic results can be affected for up to 2 years after lymphography
- Interferes with radioactive iodine uptake by thyroid tissue and may impair visualization of thyroid scintigraphy and reduce effectiveness of iodine 131 treatment
Overdose
- Overdose may lead to respiratory, cardiac or cerebral complications, which can potentially be fatal
- Microembolisms to multiple organs may occur more frequently after overdose
- Promptly initiate symptomatic treatment and support of vital functions
Pregnancy and lactation
Pregnancy category: C
Lactation: Excreted in human milk; avoid use in breastfeeding women because of risk of hypothyroidism in breastfed infants
If breastfeeding is continued, the neonate’s thyroid function should be monitored
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Lipiodol (ethiodized oil)
Mechanism of action
Iodinated contrast agent organically combined with ethyl esters of poppy seed oil fatty acids
Metabolism
Following intra-arterial administration, ethiodized oil retained in normal hepatic parenchyma is phagocytized by the Kupffer cells of the liver and washed out via the hepatic lymphatic system in about 2-4 weeks
In hepatocellular carcinoma, retention in the liver tumor is prolonged, allowing reimaging of the tumor for 4 weeks or longer
